A dual-function [Ru(bpy)3]2+ encapsulated metal organic framework for ratiometric Al3+ detection and anticounterfeiting application.

In this work, a novel composite material (HPU-24@Ru) has been prepared by combining a blue-emission Cd-based metal-organic framework (MOF, [Cd2(TCPE)(DMF)(H2O)3]n, HPU-24) with a red-emission tris (2,2'-bipyridine) dichlororuthenium(II) hexahydrate ([Ru(bpy)3]2+) molecule for ratiometric fluorescence sensing of Al3+ ions in aqueous medium and high-level dynamic anticounterfeiting application. The luminescence measurement results indicated that the fluorescence intensity of HPU-24 at 446 nm showed a red shift in the presence of Al3+ ions, and the new peak appeared at 480 nm and continued to increase with an increase in Al3+ ion concentration. Meanwhile, the fluorescence intensity of [Ru(bpy)3]2+ almost showed no change. The detection limit was calculated as 11.63 µM, which was better than that for the MOF-based Al3+ ions in some reported examples in aqueous media and achieved through strong electrostatic interactions between HPU-24@Ru and Al3+ ions. Moreover, owing to the particularity of the tetrastyryl structure in HPU-24, HPU-24@Ru showed intriguing temperature-dependent emission behavior. This unique structure provides the composite material HPU-24@Ru with attributes for high-level information encryption that make it difficult for counterfeiters to identify all of the right decryption measures.

The psychometric properties of the Chinese version of the Parkinson Anxiety Scale (C-PAS) among Parkinson's disease.

BACKGROUND: Anxiety disorder is a common non-motor symptom among individuals with Parkinson's disease (PD). At present, there are no specific tools in China for assessing the anxiety level of patients with PD. This study aimed to test the reliability and validity of the Chinese version of the Parkinson Anxiety Scale (C-PAS) in Chinese patients with PD. METHODS: A total of 158 patients with PD at one hospital in Nanjing were recruited through convenience sampling. The C-PAS was translated into Chinese using a classic 'forward-backward' translation method. Reliability tests included internal consistency and test-reliability. And in addition to content, structure and criterion-related validity were performed for the validity tests. Criterion-related validity was evaluated with the Hospital Anxiety and Depression Scale-Anxiety Subscale (HADS-A). RESULTS: Results confirmed the three-factor structure of the original C-PAS with 12 items, including persistent anxiety (5 items), episodic anxiety (4 items) and avoidance behavior (3 items). Significant and positive correlations were obtained between C-PAS and HADS-A (r = 0.82, P<0.01). The Cronbach's α and test-retest reliability of the total scale were 0.89 and 0.84, respectively. CONCLUSION: The C-PAS has demonstrated good psychometric properties. Therefore, it can be employed in patients with PD to evaluate the condition of anxiety.

Refocus on Immunogenic Characteristics of Convalescent COVID-19 Challenged by Prototype SARS-CoV-2.

BACKGROUND: Mass basic and booster immunization programs effectively contained the spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, also known as COVID-19. However, the emerging Variants of Concern (VOCs) of COVID-19 evade the immune protection of the vaccine and increase the risk of reinfection. METHODS: Serum antibodies of 384 COVID-19 cases recovered from SARS-CoV-2 infection were examined. Correlations between clinical symptoms and antibodies against VOCs were analyzed. RESULT: All 384 cases (aged 43, range 1-90) were from 15 cities of Guangdong, China. The specific IgA, IgG, and IgM antibodies could be detected within 4-6 weeks after infection. A broad cross-reaction between SARS-CoV-2 and Severe Acute Respiratory Syndrome Coronavirus, but not with Middle East Respiratory Syndrome Coronavirus was found. The titers of neutralization antibodies (NAbs) were significantly correlated with IgG (r = 0.667, p < 0.001), but showed poor neutralizing effects against VOCs. Age, fever, and hormone therapy were independent risk factors for NAbs titers reduction against VOCs. CONCLUSION: Humoral immunity antibodies from the original strain of COVID-19 showed weak neutralization effects against VOCs, and decreased neutralizing ability was associated with initial age, fever, and hormone therapy, which hindered the effects of the COVID-19 vaccine developed from the SARS-CoV-2 prototype virus.

Congenital nephrogenic diabetes insipidus arginine vasopressin receptor 2 gene mutation at new site: A case report.

BACKGROUND: Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary disorder. It is associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene and aquaporin 2 (AQP2) gene, and approximately 270 different mutation sites have been reported for AVPR2. Therefore, new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease. We report a case of a novel AVPR2 gene mutation locus and a new clinical mani-festation. CASE SUMMARY: We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth. Laboratory tests showed electrolyte disturbances and low urine specific gravity, and imaging tests showed no abnormalities. Genetic testing revealed a novel X-linked recessive missense mutation, c.283 (exon 2) C>T (p.P95S). This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence. The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation. The treatment strategy for this patient was divided into two stages, including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothia-zide (1-2 mg/kg) after a clear diagnosis. After follow-up of one and a half years, the patient gradually improved. CONCLUSION: AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.

Triploid cultivars of Cymbidium act as a bridge in the formation of polyploid plants.

Triploid is considered a reproductive barrier and also a bridge in the formation of polyploids. However, few reports are available in Cymbidium. In this study, diploid 'Xiaofeng', sexual triploid 'Yuchan' and 'Huanghe' of Cymbidium were used to evaluate hybridization compatibility of the triploids. Results showed that the sexual triploids were fertile whether they were used as male or female parents. 'Yuchan' produced male gametes of 1x, 1x~2x, 2x, 2x~3x, and 3x at frequencies of 8.89%, 77.78%, 6.67%, 3.33%, and 3.33%, respectively; while 'Huanghe' produced 3.33% 1x, 80.00% 1x~2x, 8.89% 2x, 5.56% 2x~3x, and 2.22% 3x male gametes. The cross of 'Xiaofeng' with 'Yuchan' produced progenies with a wide range of ploidy levels, including one diploid, 34 2×~3× aneuploids, 12 triploids, and one tetraploid, indicating that male gametes produced by sexual triploid were fertile and could be transmitted and fused with egg cells. On the other hand, 10 progenies obtained from the cross of 'Yuchan' × 'Xiaofeng' were all aneuploids. The cross of 'Yuchan' with 'Huanghe' produced 40 progenies including three 2×~3× aneuploids, nine 3×~4× aneuploids, 21 tetraploids, six 4×~5× aneuploids, and one pentaploid, suggesting that 2x gametes, instead of the unreduced ones played a more important role in the formation of tetraploids. The survival rates of the hybrids were all above 80.00%, with the tetraploids at 96.67%. Cytological analysis revealed that during meiosis of sexual polyploids, two chromosome sets of the 2n gamete were inclined to enter into the same daughter cell, resulting in the production of 2x gametes. Our results indicate that the triploid cymbidiums are not reproductive barrier but serve as a bridge in the formation of polyploid plants.

Convergent Genomic Signatures of Cashmere Traits: Evidence for Natural and Artificial Selection.

Convergent evolution provides powerful opportunities to investigate the genetic basis of complex traits. The Tibetan antelope (Pantholops hodgsonii) and Siberian ibex (Capra sibirica) belong to different subfamilies in Bovidae, but both have evolved similar superfine cashmere characteristics to meet the cold temperature in plateau environments. The cashmere traits of cashmere goats underwent strong artificial selection, and some traces of domestication also remained in the genome. Hence, we investigated the convergent genomic signatures of cashmere traits between natural and artificial selection. We compared the patterns of convergent molecular evolution between Tibetan antelope and Siberian ibex by testing positively selected genes, rapidly evolving genes and convergent amino acid substitutions. In addition, we analyzed the selected genomic features of cashmere goats under artificial selection using whole-genome resequencing data, and skin transcriptome data of cashmere goats were also used to focus on the genes involved in regulating cashmere traits. We found that molecular convergent events were very rare, but natural and artificial selection genes were convergent enriched in similar functional pathways (e.g., ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway) in a variety of gene sets. Type IV collagen family genes (COL4A2, COL4A4, COL4A5, COL6A5, COL6A6) and integrin family genes (ITGA2, ITGA4, ITGA9, ITGB8) may be important candidate genes for cashmere formation and development. Our results provide a comprehensive approach and perspective for exploring cashmere traits and offer a valuable reference for subsequent in-depth research on the molecular mechanisms regulating cashmere development and fineness.

Refocus on Immunogenic Characteristics of Convalescent COVID-19 Challenged by Prototype SARS-CoV-2.

Background: Mass basic and booster immunization programs effectively contained the spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, also known as COVID-19. However, the emerging Variants of Concern (VOCs) of COVID-19 evade the immune protection of the vaccine and increase the risk of reinfection. Methods: Serum antibodies of 384 COVID-19 cases recovered from SARS-CoV-2 infection were examined. Correlations between clinical symptoms and antibodies against VOCs were analyzed. Result: All 384 cases (aged 43, range 1−90) were from 15 cities of Guangdong, China. The specific IgA, IgG, and IgM antibodies could be detected within 4−6 weeks after infection. A broad cross-reaction between SARS-CoV-2 and Severe Acute Respiratory Syndrome Coronavirus, but not with Middle East Respiratory Syndrome Coronavirus was found. The titers of neutralization antibodies (NAbs) were significantly correlated with IgG (r = 0.667, p < 0.001), but showed poor neutralizing effects against VOCs. Age, fever, and hormone therapy were independent risk factors for NAbs titers reduction against VOCs. Conclusion: Humoral immunity antibodies from the original strain of COVID-19 showed weak neutralization effects against VOCs, and decreased neutralizing ability was associated with initial age, fever, and hormone therapy, which hindered the effects of the COVID-19 vaccine developed from the SARS-CoV-2 prototype virus.

Cell-Permeable PROTAC Degraders against KEAP1 Efficiently Suppress Hepatic Stellate Cell Activation through the Antioxidant and Anti-Inflammatory Pathway.

Accumulating evidence indicates that oxidative stress and inflammation are involved in the physiopathology of liver fibrogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor, which regulates the expression of redox regulators to establish cellular redox homeostasis. The Nrf2 modulator can serve as a primary cellular defense against the cytotoxic effects of oxidative stress. We designed a chimeric Keap1-Keap1 peptide (KKP1) based on the proteolysis-targeting chimera technology. The KKP1 peptide not only can efficiently penetrate into the rat hepatic stellate cell line (HSC-T6) cells but also can induce Keap1 protein degradation by the ubiquitination-proteasome degradation pathway, which releases Nrf2 and promotes the transcriptional activity of the Nrf2/antioxidant response element pathway. It then activates the protein expression of the downstream antioxidant factors, the glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 (HO-1). Finally, Keap1 protein degradation inhibits the nuclear factor-kappaB inflammatory signal pathway, the downstream inflammatory factor tumor necrosis factor alpha, and the interleukin-1beta protein expression and further inhibits the expression of the fibrosis biomarker gene. The current research suggests that our designed KKP1 may provide a new avenue for the future treatment of liver fibrosis.

Metformin Hydrochloride Mucosal Nanoparticles-Based Enteric Capsule for Prolonged Intestinal Residence Time, Improved Bioavailability, and Hypoglycemic Effect.

Metformin hydrochloride enteric-coated capsule (MH-EC) is a commonly used clinical drug for the treatment of type 2 diabetes. In this study, we described a metformin hydrochloride mucosal nanoparticles enteric-coated capsule (MH-MNPs-EC) based on metformin hydrochloride chitosan mucosal nanoparticles (MH-CS MNPs) and its preparation method to improve the bioavailability and hypoglycemic effect duration of MH-EC. In intestinal adhesion study, the residue rates of free drugs and mucosal nanoparticles were 10.52% and 67.27%, respectively after cleaned with PBS buffer. MH-CS MNPs could significantly improve the efficacy of MH and promote the rehabilitation of diabetes rats. In vitro release test of MH-MNPs-EC showed continuous release over 12 h, while commercial MH-EC released completely within about 1 h in intestinal environment (pH 6.8). Pharmacokinetic study was performed in beagle dogs compared to the commercial MH-EC. The durations of blood MH concentration above 2 µg/mL were 9 h for MH-MNPs-EC versus 2 h for commercial MH-EC. The relative bioavailability of MH-MNPs-EC was determined as 185.28%, compared with commercial MH-EC. In conclusion, MH-CS MNPs have good intestinal adhesion and can significantly prolong the residence time of MH in the intestine. MH-MNPs-EC has better treatment effect compared with MH-EC, and it is expected to be a potential drug product for the treatment of diabetes because of its desired characteristics.

Computed Tomography-based Radiomics Nomogram for the Preoperative Prediction of Tumor Deposits and Clinical Outcomes in Colon Cancer: a Multicenter Study.

RATIONALE AND OBJECTIVES: To develop and validate a computed tomography (CT)-based radiomics nomogram for the preoperative prediction of tumor deposits (TDs) and clinical outcomes in patients with colon cancer. MATERIALS AND METHODS: This retrospective study included 383 consecutive patients with colon cancer from two centers. Radiomics features were extracted from portal venous phase CT images. Least absolute shrinkage and selection operator regression was applied for feature selection and radiomics signature construction. The multivariate logistic regression model was used to establish a radiomics nomogram. The performance of the nomogram was assessed by using receiver operating characteristic curves, calibration curves and decision curve analysis. Kaplan‒Meier survival analysis was used to assess the difference of the overall survival (OS) in the TDs-positive and TDs-negative groups. RESULTS: The radiomics signature was composed of 11 TDs status related features. The AUCs of the radiomics model in the training cohort, internal validation and external validation cohorts were 0.82, 0.78 and 0.78, respectively. The radiomics nomogram that incorporated the radiomics signature and clinical independent predictors (CT-N, CEA and CA199) showed good calibration and discrimination with AUCs of 0.88, 0.80 and 0.81 in the training cohort, internal validation and external validation cohorts, respectively. The radiomics nomogram-predicted high-risk groups had a worse OS than the low-risk groups (p < 0.001). The radiomics nomogram-predicted TDs was an independent preoperative predictor of OS. CONCLUSION: The radiomics nomogram based on CT radiomics features and clinical independent predictors could effectively predict the preoperative TDs status and OS of colon cancer. IMPORTANT FINDINGS: CT-based radiomics nomogram may be applied in the individual preoperative prediction of TDs status in colon cancer. Additionally, there was a significant difference in OS between the high-risk and low-risk groups defined by the radiomics nomogram, in which patients with high-risk TDs had a significantly worse OS, compared with those with low-risk TDs.

Knowledge of cervical cancer prevention and treatment, and willingness to receive HPV vaccination among college students in China.

BACKGROUND: Cervical cancer is the fourth most common cancer in women. Up to 99% of cervical cancer cases are associated with high-risk human papillomavirus (HPV). Sexual behavior is a direct risk factor for HPV infection, and sexually active college students, therefore, receive attention for HPV vaccination. At present, most Chinese studies lack of in-depth research on influencing factors, and are limited to cervical cancer, HPV, or HPV vaccine, without comprehensive consideration. This study investigated Chinese college students' cervical cancer prevention and treatment knowledge level, and explored the influencing factors, and understood their willingness to receive HPV vaccination. The findings of this study will lay a foundation for promoting the early screening of cervical cancer and vaccination process. METHODS: A total of 800 college students from four universities in Zhengzhou, China were selected by multistage random sampling method. A self-administered questionnaire on the knowledge of cervical cancer prevention and treatment, and willingness to receive HPV vaccination was carried out. A logistic regression model was conducted to analyze factors influencing knowledge of cervical cancer prevention and treatment among college students. RESULTS: Up to 87.9% of college students said they had heard of cervical cancer. The proportion of college students with good knowledge of cervical cancer prevention and treatment was 46.7%. Logistic regression showed that gender, major, grade, level of education, the father's level of education, premarital sex attitude, and mother cervical cancer screening participation had a significant influence on cervical cancer prevention and treatment knowledge level (P < 0.05). In addition, 589 (74.0%) of college students had heard of HPV vaccine, and 92.8% of college students said they were willing to get vaccinated or recommended that their relatives and friends get vaccinated. CONCLUSIONS: The knowledge level of cervical cancer prevention and treatment knowledge among college students in Zhengzhou is low. Many of them had poor knowledge about HPV vaccine, but their willingness to vaccination is high. Various health education modes should be carried out for people with different characteristics, to improve their knowledge of cervical cancer prevention and promote the vaccination process.

Heterogeneous activation of peroxymonosulfate by magnetic hybrid CuFe2O4@N-rGO for excellent sulfamethoxazole degradation: Interaction of CuFe2O4 with N-rGO and synergistic catalytic mechanism.

In order to address the low catalytic performance of magnetic CuFe2O4 caused by the agglomeration, low conductivity and potential metal ion leaching risk, N-doped reduced graphene oxide (N-rGO) with high charge density and rich active sites was employed as support to synthesize CuFe2O4@N-rGO (CuFe@NG), which was used for peroxymonosulfate (PMS) activation to degrade sulfamethoxazole (SMX). Results showed that the CuFe@NG/PMS system exhibited excellent degradation rate and mineralization efficiency on SMX in 60 min, which exceeded 93.15% and 31.96%, respectively. Besides, its degradation rate constants was 1.68 times higher than that of the CuFe2O4/PMS system. The enhanced performance could be mainly ascribed to the efficient synergistic activation of PMS by two components: I. the successful dispersion of CuFe2O4 on N-rGO and the interaction between them exposed more Fe3+-O2- and Cu2+-O2- active sites via decreasing size and aggregation of CuFe2O4 particles; II. the supported N-rGO supplied extra CO, C-OH and C-NC active groups, resulting in a large number of π electrons; III. the pyrrole N formed by further doping of N could activate the π electrons and reduce the energy barrier of electron transfer. The abundant active groups and sites and excellent electron transfer ability co-accelerate the production of active species. Specifically, surface-bound radical (•OH, SO4•-) and singlet oxygen 1O2 played a dominant role according to ESR and quenching tests. Furthermore, M-O-C binding site between two components enhanced catalyst stability and reduced metal leaching, leading to its availability on reusability in the 5 cyclic experiments. Lastly, CuFe@NG/PMS system also possessed a strong application ability in actual aquatic environment for SMX treatment.

A Pan-Transcriptome Analysis Indicates Efficient Downregulation of the FIB Genes Plays a Critical Role in the Response of Alfalfa to Cold Stress.

Alfalfa (Medicago sativa L.) is a perennial forage legume that is widely distributed throughout the world, and cold stress is an important environmental factor limiting the growth and production of alfalfa in cold regions. However, little is known of the molecular mechanisms regarding cold tolerance in alfalfa. Here, we conducted physiological metabolism assays and pan-transcriptome sequencing on eight cultivars of alfalfa under cold stress conditions. The results of the RNA-seq analysis showed that the genes are "oxidoreductase activity" and "transcription regulator activity", suggesting that genes with such functions are more likely to play important roles in the response to cold stress by alfalfa. In addition, to identify specific gene modules and hub genes in response to alfalfa cold stress, we applied weighted gene co-expression network (WGCNA) analyses to the RNA-seq data. Our results indicate that the modules of genes that focus on the ATPase complex, ribosome biogenesis, are more likely to be involved in the alfalfa response to cold stress. It is important to note that we identified two fibronectin (FIB) genes as hub genes in alfalfa in response to cold stress and that they negatively regulate alfalfa response to chilling stress, and it is possible that dormant alfalfa is more effective at down-regulating FIB expression and therefore more resistant to cold stress.

A feasibility study of noninvasive prenatal diagnosis in facioscapulohumeral muscular dystrophy type 1 in a Chinese family.

Objective: To demonstrate the feasibility of haplotype-based noninvasive prenatal diagnosis of Facioscapulohumeral Muscular Dystrophy type 1 (FSHD1). Methods: Bionano optical mapping was used to identify the D4Z4 structural variation of the genomic DNA sample from the proband affected with FSHD1. In addition, based on the technique of next generation sequencing, the pathogenic haplotype was determined by using trio strategy through genotyping his parents, and also fetal inheritance of paternal haplotypes was then deduced using the Hidden Markov Model. Results: Bionano optical mapping analysis revealed that the proband has only three D4Z4 repeats left in the 4q35 chromosomal region and a disease-permitting 4qA haplotype. The other normal allele of the proband contains 29 D4Z4 repeats and also a 4qA haplotype. The noninvasive cell-free fetal DNA (cffDNA)-based haplotype analysis suggested that the fetus inherited the pathogenic allele from his father and thus was predicted to be affected by FSHD1. In addition, Bionano optical mapping also demonstrated the presence of the pathogenic allele in the fetus by interrogating the genomic DNA from the amniotic fluid cells. Conclusion: Our study showed the cffDNA-based haplotyping was feasible for the noninvasive prenatal diagnosis of FSHD1, which is able to provide earlier testing results with a lower risk of miscarriage and infection than invasive techniques.

Role of sulfur vacancies in MoS2 monolayers in stabilizing Co atoms for efficient CO oxidation.

By performing first-principles calculations, a MoS2 monolayer with a Co atom doped at the sulfur defect (Co-SMoS2) was investigated as a single-atom catalyst (SAC) for CO oxidation. The Co atom is strongly constrained at the S-vacancy site of MoS2 without forming clusters by showing a high diffusion energy barrier, ensuring good stability to catalyze CO oxidation. The CO and O2 adsorption behavior on Co-SMoS2 surface and four reaction pathways, namely, the Eley-Rideal (ER), Langmuir-Hinshelwood (LH), trimolecular Eley-Rideal (TER) as well as the New Eley-Rideal (NER) mechanisms are studied to understand the catalytic activity of Co-SMoS2 for CO oxidation. The CO oxidation is more likely to proceed through the LH mechanism, and the energy barrier for the rate-limiting step is only 0.19 eV, smaller than that of noble metal-based SACs. Additionally, the NER mechanism is also favorable with a low energy barrier of 0.26 eV, indicating that the Co-SMoS2 catalyst can effectively promote CO oxidation at low temperatures. Our investigation demonstrates that the S-vacancy of MoS2 plays an important role in enhancing the stability and catalytic activity of Co atoms and Co-SMoS2 is predicted to be a promising catalyst for CO oxidation.

Prenatally diagnosed 16p11.2 copy number variations by SNP Array: A retrospective case series.

OBJECTIVE: The 16p11.2 copy number variations (CNVs) are increasingly recognized as one of the most frequent genomic disorders, with a broad spectrum of phenotypes. The fetal phenotype associated with 16p11.2 CNVs is poorly described. The current study presents prenatal series of 16p11.2 CNVs and provides a better understanding of this submicroscopic imbalance in prenatal diagnosis. METHOD: Retrospective case series were extracted from a single tertiary referral center performing prenatal single nucleotide polymorphism (SNP) array from April 2017 to December 2021. The maternal demographics, indication for amniocentesis, ultrasound findings, SNP array results, inheritance of the CNVs, and pregnancy outcomes were studied. RESULTS: We indentified 30 fetuses carrying 16p11.2 CNVs, representing 0.35% (30/8578) of prenatal SNP array results. The series included 17 fetuses with a proximal deletion, 7 with a distal deletion, 4 with a proximal duplication, and 2 with a distal duplication. Prenatal ultrasound anomalies were reported in 80% of these cases. The most common presentation was vertebralanomalies (9/30). Other features noted in more than one fetus were increased nuchal translucency/nuchal fold (NT/NF) (5/30), absent/hypoplastic nasal bone (3/30), polyhydramnios (3/30), ventricular septal defect (VSD) (2/30), unilateral mild ventriculomegaly (2/30), fetal growth restriction (FGR) (2/30), right aortic arch (2/30). All the 9 vertebralanomalies were present in fetuses harboring proximal deletion (9/17). Familial transmission was confirmed in 44% of cases (11/25) and termination of pregnancy was requested in 62.1% (18/29) of cases. CONCLUSION: The 16p11.2 CNVs can have variable prenatal phenotypes and these CNVs are frequently inherited from parents with a milder or normal phenotype. Our results underline that vertebral deformities were frequent in cases of 16p11.2 proximal deletion, and further demonstrate the incomplete penetrance of the CNVs.

Impact on the antioxidant system, histology, and cell death of zebrafish liver after exposure to industrial sludge leachate.

The improper disposal of sludge is a still-present phenomenon in China. The leachate formed at the bottom of the sludge pile would cause toxicological effects on aquatic organisms and affect the health of humans by entering the surrounding rivers and groundwater. In this study, the hepatotoxicity of zebrafish induced by sludge leachate was assessed by antioxidant enzyme activities, semi-quantitative histopathological assessment, and TUNEL apoptosis assay. The results indicated that the leachate would induce oxidative stress and eventually lead to an increase in lipid peroxide after a 7-day exposure. The histopathological indexes demonstrated that exposure to leachate would cause histological damage by circulatory disturbances, regressive changes, progressive changes, and inflammatory responses. According to the TUNEL results, it could be inferred that apoptotic hepatocytes increased after exposure for 7 days due to oxidative stress and histological damage. Overall, this study provided a valuable approach to assessing the toxic effects of sludge leachate and described the underlying mechanism of leachate-induced hepatotoxicity in zebrafish. This work will generate new insights into the ecological toxicity of leachate and promote the development of sludge disposal in China.

CT-based radiomics nomogram for the preoperative prediction of lymphovascular invasion in colorectal cancer: A multicentre study.

OBJECTIVE: To develop and externally validate a CT-based radiomics nomogram for the preoperative prediction of lymphovascular invasion (LVI) in patients with colorectal cancer (CRC). METHODS: 357 patients derived from two centres with pathologically confirmed CRC were included in this retrospective study. Two-dimensional (2D) and three-dimensional (3D) radiomics features were extracted from portal venous Phase CT images. The least absolute shrinkage and selection operator algorithm and logistic regression were used for constructing 2D and 3D radiomics models. The radiomics nomogram was developed by integrating the rad-score and the clinical risk factor. RESULTS: The rad-score was significantly higher in the LVI + group than in the LVI- group (p < 0.05). The AUC, accuracy, sensitivity and specificity of the 3D radiomics model were higher than those of the 2D radiomics model. The AUCs of 3D and 2D radiomics models in the training set were 0.82 (95% CI: 0.75-0.89) and 0.74 (95% CI: 0.66-0.82); in the internal validation set were 0.75 (95% CI: 0.65-0.85) and 0.67 (95% CI: 0.56-0.78); in the external validation set were 0.75 (95% CI: 0.64-0.86) and 0.57 (95% CI: 0.45-0.69); respectively. The AUCs of the nomogram integrating the optimal 3D rad-score and clinical risk factors (CT-reported T stage, CT-reported lymph node status) in the internal set and external validation set were 0.82 (95% CI: 0.73-0.91) and 0.80 (95% CI: 0.68-0.91), respectively. CONCLUSIONS: Both 2D and 3D radiomics models can predict LVI status of CRC. The nomogram combining the optimal 3D rad-score and clinical risk factors further improved predictive performance. ADVANCES IN KNOWLEDGE: This is the first study to compare the difference in performance of CT-based 2D and 3D radiomics models for the preoperative prediction of LVI in CRC. The prediction of the nomogram could be improved by combining the 3D radiomics model with the imaging model, suggesting its potential for clinical application.

A microfluidic demonstration of "cluster-sprout-infiltrating" mode for hypoxic mesenchymal stem cell guided cancer cell migration.

Mesenchymal stem cells (MSCs) play a critical role in tumor metastasis. However, the dynamic process of MSCs-mediated cancer cell invasion remains inconclusive. In breast cancer mouse models, we observed that MSCs promoted lung metastasis. We constructed a microfluidic-based 3D co-culture device to monitor MSCs-mediated cancer cell invasion in a nutrient-deficient hypoxic microenvironment. On biomimetic microfluidic devices, MSCs guided cancer cell migration in a "cluster-sprout-infiltrating" mode. Importantly, hypoxic conditions significantly promoted MSCs migration at the infiltration stage, leading to accelerated breast cancer cell invasion. Moreover, hypoxia related LncRNA analysis showed that H19 was dramatically upregulated in response to hypoxic conditions. Conversely, H19 depletion impaired MSCs-directed breast cancer cell invasion. Mechanistically, H19 functions as a competitive endogenous RNA (ceRNA) which sequesters miRNA let-7 to release its target matrix metalloproteinase-1 (MMP1). Intriguingly, aspirin dramatically suppressed H19 and MMP1 expression and blocked MSCs infiltration under hypoxic conditions, resulting in alleviated breast cancer cell invasion. These findings point to the metastatic promoting role of MSCs in tumor stroma and suggest that MSCs might be a therapeutic target for metastatic breast cancer.

Observation of high-order imaginary Poynting momentum optomechanics in structured light.

The imaginary Poynting momentum (IPM) of light has been captivated as an unusual origin of optical forces. However, the IPM force is predicted only for dipolar magnetoelectric particles that are hardly used in optical manipulation experiments. Here, we report a whole family of high-order IPM forces for not only magnetoelectric but also generic Mie particles, assisted with their excited higher multipoles within. Such optomechanical manifestations derive from a nonlocal contribution of the IPM to the optical force, which can be remarkable even when the incident IPM is small. We observe the high-order optomechanics in a structured light beam, which, despite carrying no angular momentum, is able to set normal microparticles into continuous rotation. Our results provide unambiguous evidence of the ponderomotive nature of the IPM, expand the classification of optical forces, and open new possibilities for levitated optomechanics and micromanipulations.